Pharmaceutical compositions may be administered by inhalation to or through the lung of a patient.
Typical pharmaceutical compositions combine pharmacologic activity with pharmaceutical properties, and may be delivered by means of a delivery device (such as a dry powder inhaler) to the targeted pulmonary system of a subject of treatment.
A combination of intrinsic physicochemical properties and other particle characteristics (e.g. shape and surface area) affects the interactive forces and aerodynamic properties of these particles within such formulations. These important properties in turn affect fluidization, dispersion, delivery, and ultimately deposition in the peripheral airways and lungs.
Commonly, in dry powder formulations, a dose of the pharmaceutical composition is positioned within an aerosolization chamber, where it is to be aerosolized. Such compositions are therefore required to be easily and highly aerosolizable in order to clear the composition from the inhaler device. Subsequently, the aerosolized particles are dispersed into a respirable form by means of an airflow provided by a pressurized source of gas, or by the patient's own respiratory effort. Estimates of aerosolizibility and dispersibility may be made by measuring the emitted dose and fine particle fraction of the composition, respectively.
To enable aerosolized particles to settle in the targeted regions of the lung associated with local and/or systemic drug delivery, the particle size must be carefully considered. In general, one of the main factors which determines the average particle size of a powdered composition is the selection of a suitable process from existing powder technologies. In addition, if the cohesive forces (which are dependent on the size of particles) acting on the powder are pronounced, the designed shear of a provided airflow may not be sufficient to separate an included drug from the carrier particles, and will subsequently result in low deposition efficiencies within the targeted areas of the pulmonary system.
In general, particles which are of an aerodynamic diameter greater than 5 μm generally tend to be deposited within the mouth or throat, and therefore offer little therapeutic benefit to a patient. In contrast, particles having an aerodynamic diameter smaller than 0.5 μm generally do not settle out of a provided air flow to stay deposited in the lungs, and may undesirably be exhaled by a patient administered such a formulation.
There is therefore a need to provide formulations which are better designed for inhalation that overcome, or at least ameliorate, one or more of the disadvantages of existing inhaled-formulations as described above.